This study will determine which characteristics of virus and host cells favor the binding, penetration, and retrograde axoplasmic transport of herpes simplex virus (HSV) in neurons. These investigations will focus on the early virus-cell interactions which allow HSV to reach the neuronal soma and establish latency. These studies will also contribute new information on the axoplasmic transport of foreign proteins. If transport of viral components (envelope glycoproteins, for example) can be documented, it is planned to package anti-viral drugs within membranes containing these subunits, so that they also will be transported to the cell body and gain access to the viral DNA. These investigations will combine biochemical and electron microscopic (including radioautography and immunocytochemistry) techniques to determine the molecular features of HSV required for uptake and/or retrograde axoplasmic transport. The specfic host cell receptor in cultured neuroblastoma cells will also be characterized.